The overall objective of this research project is to clarify how calcium (and other ions) affect the amount and time course of neurotransmitter release from depolarized presynaptic nerve terminals. Focal extracellular and intracellular techniques will be used to record synaptic potentials from frog and snake surface mFtor nerve terminals, while calcium and other ions are iontophoretically applied. Nerve stimulation and iontophoretic patterns will be controlled by an on-line computer. Specific projects include: (1) a reinvestigation of whether the calcium which activates neurotransmitter release enters the nerve terminal during the nerve action potential, during the synaptic delay, or coincident with transmitter release; (2) characterization of the effects of various ions an drugs on the time course of evoked neurotransmitter release, in an attempt to clarify how these agents affect the presynaptic release mechanisms; and (3) a semiquantitative characterization of the effects of calcium on historical effects of repetitive nerve stimulation such as facilitation, augmentation and potentiation, in an attempt to determine whether residual intraterminal calcium mediates any or all of these phenomena. BIBLIOGRAPHIC REFERENCES: E. F. Barrett & J.N. Barrett. Separation of two voltage-sensitive potassium currents, and demonstration of a tetrodotoxin-resistant calcium current in frog motoneurones. J. Physiol. 37 pp. 1976, in press.